title: Imaging and therapy with rituximab anti-CD20 immunotherapy in an animal model of central nervous system lymphoma.
abstract: OBJECTIVE
  To evaluate the effect of rituximab monoclonal antibody (mAb) on MRI tumor volumetrics and efficacy in a rat model of central nervous system (CNS) lymphoma when delivery to the brain was optimized with osmotic blood-brain barrier disruption (BBBD).
  
  
  METHODS
  Female nude rats with intracerebral MC116 human B-cell lymphoma xenografts underwent baseline MRI and were randomized into 5 groups (n = 6 per group): (i) BBBD saline control; (ii) methotrexate with BBBD; (iii) rituximab with BBBD; (iv) rituximab and methotrexate with BBBD; and (v) intravenous rituximab. Tumor volumes were assessed by MRI at 1 week, and rats were followed for survival.
  
  
  RESULTS
  BBBD increased delivery of yttrium-90-radiolabeled mAb in the model of CNS lymphoma. Control rats showed 201 ± 102% increase in tumor volume on MRI 1 week after entering the study and median 14-day survival (range: 6-33). Tumor growth on MRI was slowed in the methotrexate treatment group, but survival time (median: 7 days; range: 5-12) was not different from controls. Among 17 evaluable rats treated with rituximab, 10 showed decreased tumor volume on MRI. All rituximab groups had increased survival compared with control, with a combined median of 43 days (range: 20-60, P < 0.001). There were no differences by route of delivery or combination with methotrexate.
  
  
  CONCLUSIONS
  Rituximab was effective at decreasing tumor volume and improving survival in a model of CNS lymphoma and was not affected by combination with methotrexate or by BBBD. We suggest that rituximab warrants further study in human primary CNS lymphoma.
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Muldoon
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Lewin
authors.forename: Edit
authors.initials: E
authors.lastname: Dósa
authors.forename: Dale F
authors.initials: DF
authors.lastname: Kraemer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pagel
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Doolittle
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008727:Methotrexate / Q000008:administration & dosage; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D015021:Yttrium Radioisotopes; D000069283:Rituximab; D008727:Methotrexate